The Physicomechanical Deterioration Characteristics and Mesoscopic Damage Analysis of Sandstone under Acidic Environment

The physicomechanical deterioration characteristics of sandstone subjected to H2SO4, HCl, and H2O solutions of different pH values are studied by the method of long-term accelerated immersion. The quantitative relationships between the damage variables based on CT (computer tomographic identification technology) numbers and the immersion time, the uniaxial compressive strength, the peak point strain, and the elastic modulus of rock samples are analyzed. The test results indicate that the pH value of immersion solutions, the dissolution rate of Ca2+ and Na+, and the quality change of rock samples show visible stage characteristics under acidic environment. With the soaking time extended, the pH value of solutions increases gradually, and the quality change of rock samples decreases gradually. The smaller the pH value of immersion solutions is, the higher the dissolution rate of Ca2+ and Na+ is. However, the cation dissolution rate under a weak acid environment with a high pH value has little difference with that under the distilled water (pH = 7). With the increase of the soaking time and the acidity, the compaction stage of rock samples becomes longer, the elastic stage becomes shorter, the deterioration degree of mechanical parameters becomes more extensive, and the destruction of sandstone samples shows ductility characteristics increasingly. The corrosion degree of corroded sandstone samples is quantitatively represented by microscopic damage variables based on CT numbers. The regression analysis results show that damage variables of acid-corroded sandstone samples have a power function relationship with soaking time and an exponential function relationship with peak strength, peak point strain, and elastic modulus

Experimental Study on Physicomechanical Properties of Sandstone under Acidic Environment

The influence of acid solution and immersion time on the physicomechanical properties of sandstone is investigated. Uniaxial compression tests on sandstone samples are conducted to determine the variations of relative mass, deformation, and strength characteristics of sandstone subjected to different pH sulfuric acid corrosion values. The changes of pH and Mg2+ and Ca2+ concentration of immersion solutions are monitored during soaking. The corrosion mechanism of sandstone attacked by the acid solution is discussed with the results of SEM tests. Based on the nondestructive CT scanning test, the damage variables of acid-corroded sandstone are deduced, and the damage degree of sandstone is quantitatively analyzed. The results indicate that the deformation characteristics of sandstone samples under acid attack are characterized by the softening of rock, and the softening degree gradually increases with the increase of the acidity and the soaking time. The peak strength of sandstone samples declines as soaking time extends. The chemical effects lead to a large amount of dissolution of the rock mineral assemblage, resulting in the large-scale development of the pores inside the rock, which changes the macroscopic mechanical properties. The damage variables of acid corrosion sandstone based on CT numbers are deduced, and the quantitative relationship between damage variables and immersion time is established, which provides a basis for constructing a damage constitutive model of sandstone in the acidic environment

SHARP1 suppresses angiogenesis of endometrial cancer by decreasing hypoxia-inducible factor-1α level.

Recent data support a role for SHARP1, a basic helix-loop-helix transcription repressor, in the regulation of malignant cell behavior in several human cancers. However, the expression and role of SHARP1 during the development of endometrial cancer (EC) remain unclear. Here we show that upregulation of SHARP1 suppressed tumor angiogenesis by decreasing hypoxia-inducible factor-1α (HIF-1α), inhibited cell viability and tumor growth in EC. Immunohistochemical staining showed that the expression of SHARP1 was negatively correlated with tumor stage, histological grade, myometrial invasion, lymph node metastasis, blood vessel permeation in the myometrium and HIF-1α expression. Mechanistic studies showed that SHARP1 interacted with HIF-1α physically, and the protein level of HIF-1α and the mRNA level of its target genes (VEGFA, ANGPTL4 and CA9) were decreased by SHARP1 under hypoxia. Upregulation of SHARP1 in EC impeded hypoxia-induced angiogenesis by reducing VEGF secretion. Immunohistochemical analysis verified a correlation between decreased SHARP1 expression and increased microvessel density in EC tissues. Additionally, SHARP1 inhibited cell viability in EC cell lines. Overexpression of SHARP1 in vivo inhibited tumor growth and angiogenesis, and decreased HIF-1α expression. In this study, we established SHARP1 as a novel tumor suppressor of EC and shed light on the mechanisms by how SHARP1 inhibited EC progression. Therefore, SHARP1 may be a valuable prognostic biomarker for EC progression and shows promise as a new potential target for antiangiogenic therapeutics in human EC

SHARP1 inhibits cell viability in EC cell lines.

<p>MTT assay was conducted at each time point to quantify cell viability for Ishikawa cells transfected with control or SHARP1 expression plasmid (A) and for RL95-2 cells transfected with control or SHARP1 siRNA (B). Data represent the mean ± SD from one representative experiment of three independent experiments, each performed in triplicate (***<i>P</i><0.001).</p

Primer sequences for qPCR.

<p>Primer sequences for qPCR.</p

SHARP1 inhibits angiogenesis.

<p>(A) The concentration of VEGF in the CMs collected from Ishikawa cells transfected with empty plasmid (1.6 µg/ml) under normoxia (N) and hypoxia (H), or Ishikawa cells transfected with SHARP1 full-length plasmid (1.6 µg/ml) under normoxia (N + S) and hypoxia (H + S) were determined by ELISA. Viability (B), trans-well migration (C) and tube formation (D) of HUVECs, and Matrigel plug assays (E) using the CM described above. (B) MTT and (C) migration assays were performed 24 h after incubation. (D) 96-well dishes were coated with Matrigel, and HUVEC tube formation assays were performed 14 h after incubation. Left, representative photographs are shown at 100× magnification (scale bar, 200 µm). Right, the relative total tube length formed under the indicated conditions. Matrigel plug assays were performed using CMs (E) or corresponding Ishikawa cells described above (F). CMs (100 µl) or cells (1×10⁶ per injection) mixed with Matrigel (300 µl) were inoculated into the flank of a nude mouse, and the Matrigel plug was excised 14 days later. Left, representative Matrigel plugs. Right, relative MVD as determined by immunohistochemical staining for CD34. Data represent the mean ± SD from one representative experiment of three independent experiments, each performed in triplicate (*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001). (G) Representative photographs of CD34 staining in various endometrium tissue specimens (magnification, 400×; scale bar, 50 µm). (H) Spearman’s correlation test was used to analyze the correlation of SHARP1 immunostaining levels and MVD (based on CD34 staining) from 16 EC specimens using SPSS software.</p

SHARP1 inhibits tumor growth, HIF-1α expression and angiogenesis in tumor xenografts.

<p>(A) Stable transfection of Ishikawa cells with empty lentiviral vectors or lentiviral vectors carrying human SHARP1 gene. Left panels showed morphology of Ishikawa cells under light microscope (upper) or fluorescence microscope (lower) in the same field (magnification: 200×; scale bar: 100 µm), and right panels showed transfection efficiency confirmed by qPCR and western blotting. Ishikawa cells transfected with Lenti-Control or Lenti-SHARP1 were injected subcutaneously into the flank of each mouse. (B) The mean tumor volume was measured by calipers on the indicated days. (C) Photographs of tumors excised 42 days after inoculation of stably transfected cells into nude mice. (D) Tumor weight (left) and volume (right) of each nude mouse at the end of 42 days. (E) Left: Representative microphotographs of H&E, SHARP1 and HIF-1α staining in nude mice tumor tissues (magnification: 400×; scale bar: 50 µm); Right: Statistical analysis of SHARP1 and HIF-1α staining in nude mice tumor tissues. (F) For evaluation of the proliferation index and angiogenic index, the Ki-67-stained nuclei and CD34-positive blood vessels in the hotspot areas were counted at 400× magnification. Representative photographs were taken at 400× magnification (scale bar, 50 µm). Data represent the mean ± SD of 5 grafts in each condition (**<i>P</i><0.01, ***<i>P</i><0.001).</p